A new resource for Caenorhabditis elegans experimental evolution and quantitative trait mapping, the C. elegans multiparent experimental evolution (CeMEE) panel of recombinant inbred lines. Chromosome IV haplotypes are shown colored by origin from 16 founders, and lines are ordered by chromosome-wide genetic similarity (or by mating system: low diversity lines from populations evolved under predominant selfing are clustered uppermost). The path to super-model system for C. elegans began over a century ago, and the first known drawing of an adult hermaphrodite, modified from Maupas (1900), is shown overlaid. A history of early (pre-Brenner) research, required reading for any worm student, can be found in Nigon and Félix (2017). Background image courtesy of Luke Noble. See Noble et al. pp 1665–1687.

Check out the December issue of GENETICS by looking at the highlights or the full table of contents!

ISSUE HIGHLIGHTS

Gene Conversion Facilitates Adaptive Evolution on Rugged Fitness Landscapes, pp. 1577–1589

Philip Bittihn and Lev S. Tsimring

An important question in evolutionary theory is how adaptation might be hindered on a rugged fitness landscape in the presence of strong selection that only allows beneficial mutations to fix. Bittihn and Tsimring predict that recurrent gene conversion between an original gene and its silenced copy helps to circumvent fitness valleys and can therefore accelerate adaptive evolution. Stochasticity in finite populations further increases the effectiveness of the proposed mechanism. Their results shed new light on the contribution of pseudogenes to adaptive evolution.

Long-Term Fragility of Y Chromosomes Is Dominated by Short-Term Resolution of Sexual Antagonism, pp. 1621–1629

Heath Blackmon and Yaniv Brandvain

Existing models of sex chromosome evolution do not address whether inversions can accumulate even if they cause difficulties in meiotic pairing. Blackmon and Brandvain’s population genetic model shows that inversions fix more easily when male-benefit alleles are dominant and that inversions on the Y chromosome fix with lower selection coefficients than comparable X chromosome inversions. They show that sex chromosome inversions can invade and fix despite causing a substantial increase in the risk of aneuploidy, concluding that sexual antagonism can both 1) lead to an increased risk of sex chromosomes aneuploidy and 2) favor diverse mechanisms to reduce aneuploidy.

Testing Genetic Pleiotropy with GWAS Summary Statistics for Marginal and Conditional Analyses, pp. 1285–1299

Yangqing Deng and Wei Pan

The ability to detect pleiotropy has important biological applications, but there is a lack of rigorous tests available. One exception is a recent test proposed by Schaid et al., which can only be applied 1) to marginal analysis (that cannot distinguish direct and indirect effects) and 2) to individual-level genotypic and phenotypic data (which may not be available for large GWAS). Here, Deng and Pan extend this test to address these two aspects, largely expanding the scope of applications of pleiotropy testing.

Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the Atypical MAP Kinase MAPK15 in Caenorhabditis elegans and Human Cells, pp. 1423–1440

Anna Kazatskaya, Stefanie Kuhns, Nils J. Lambacher, Julie E. Kennedy, Andrea G. Brear, Gavin J. McManus, Piali Sengupta, and Oliver E. Blacque

Kazatskaya et al. uncover a role for the atypical MAP kinase MAPK15 in regulating primary cilium structure and morphology in both C. elegans and human cells. They find that MAPK15 localizes to a discrete subdomain of the basal body, regulating the distribution of a variety of ciliary proteins. Their results describe a new primary cilia-related role for a poorly studied member of the MAPK family in vivo, indicating a broad requirement for this kinase in the formation of multiple ciliary classes across species.

Distinguishing Among Modes of Convergent Adaptation Using Population Genomic Data, pp. 1591–1619

Kristin M. Lee and Graham Coop

Cases of convergent adaptation demonstrate the power of natural selection and can be used as an important tool for studying the molecular and ecological basis of adaptation. Understanding the mode of convergence addresses fundamental questions in evolutionary biology, such as how often adaptation is mutation limited and the roles of standing variation and gene flow. Lee and Coop present a model-based statistical approach that utilizes genomic data to identify loci involved in convergence and distinguishes among alternate modes.

Polygenicity and Epistasis Underlie Fitness-Proximal Traits in theCaenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panel, pp. 1663–1685

Luke M. Noble, Ivo Chelo, Thiago Guzella, Bruno Afonso, David D. Riccardi, Patrick Ammerman, Adel Dayarian, Sara Carvalho, Anna Crist, Ania Pino-Querido, Boris Shraiman, Matthew V Rockman, and Henrique Teotónio

Using a new experimentally evolved multiparent mapping resource for C. elegans, Noble et al. have outlined the genetic architecture of worm fertility and adult size. Abundant variance remained after more than 250 generations of lab adaptation and, as expected for traits aligned with fitness, some of this was explained by alleles with weak additive effects distributed throughout the genome. A handful of large effect interactions exhibiting sign epistasis explained as much variance as genomic background, despite generally weak global population structure among C. elegans wild isolates.

Pyridoxine-Dependent Epilepsy in Zebrafish Caused by Aldh7a1 Deficiency, pp. 1501–1518

Izabella A. Pena, Yann Roussel, Kate Daniel, Kevin Mongeon, Devon Johnstone, Hellen Weinschutz Mendes, Marjolein Bosma, Vishal Saxena, Nathalie Lepage, Pranesh Chakraborty, David A. Dyment, Clara D. M. van Karnebeek, Nanda Verhoeven-Duif, Tuan Vu Bui, Kym M. Boycott, Marc Ekker, and Alex MacKenzie

Pyridoxine-dependent epilepsy (PDE) is a severe neonatal seizure disorder and is here modeled in aldh7a1 -/- zebrafish. Mutant larvae display spontaneous and recurrent seizures which can be alleviated by vitamin B6 treatment. Biochemical analysis using mass spectrometry reveals low levels of B6 vitamers and alteration in several amino acids, especially lysine metabolites. Remarkably, the mutant fish have reduced GABA levels. In sum, Pena et al. offer insights into disease pathophysiology and report the first PDE animal model, opening new paths for drug discovery.

Reconstructing the Molecular Function of Genetic Variation in Regulatory Networks, pp. 1699–1709

Roni Wilentzik, Chun Jimmie Ye, and Irit Gat-Viks

Genetic studies have recognized hundreds of genomic quantitative trait loci as potential contributors to inherited transcriptional variation in response to stimulations. Such “reQTLs” commonly affect the transduction of signals along the regulatory network that controls gene transcription. Wilentzik, Ye, and Gat-Viks developed an algorithm that simultaneously identifies both a reQTL and the particular pathway through which this reQTL affects downstream signal transduction along the network. Using synthetic datasets, they show that the algorithm improves existing pathway-identification and reQTL-identification methods and demonstrate its ability to identify reQTL-perturbed pathways in mouse and human immune dendritic cells.

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